The broad, long-term objective is the development of a theory of infectious disease epidemiology, or theory of dependent happenings, that relates population dynamics of infectious disease to study design and analysis of observations on individuals. The specific aims of this proposal are to develop methods for planning and evaluating interventions against malaria in the field taking into account . relevant differences between migration-induced and holoendemic malaria, . indirect effects on estimates of efficacy measures, . heterogeneities in vector and human host populations for interpreting outcome measures, and . extension of these methods where applicable to other infectious diseases, in particular dengue and other vector-borne diseases. The experimental design and methods consists of a theoretical part- . conceptual, mathematical and statistical development of efficacy and effectiveness parameters in based on robust transmission models, and . deterministic and stochastic computer simulations for sensitivity analysis of parameters and prediction- and an applied part- . in collaboration with the Malaria Branch, CDC, design and analysis of a population-based, cohort follow-up intervention study in a holoendemic area of Africa, and . in collaboration with members of the Oswaldo Cruz Foundation, design and analysis of a targeted intervention against migration-induced malaria in the Amazon.